Method for producing aminofluorinating agent and aminofluorinated product

Abstract

The present invention is a compound represented by general formula (A) [in the formula, G is -SO2R1, -CO-G1, or -C(CH3)-Ph; R1 is a C1-30 alkyl group which may have a halogen atom or a phenyl group which may have a substituent; G1 is a heteroaryl group which may have a substituent or -CG11G12-G13; G11 and G12 are each independently a hydrogen atom, a C1-3 alkyl group, an alkoxy group, or a fluoroalkyl group; G13 is a phenyl group which may have a substituent; and Ph is a phenyl group].

Description

[Technical Field]

[0001] The present invention relates to an amino fluorinating agent that introduces a protected amino group, and a method for producing an amino fluorinated product using the amino fluorinating agent. This application claims priority based on Japanese Patent Application No. 2021-154618, filed in Japan on September 22, 2021, and Japanese Patent Application No. 2022-046931, filed in Japan on March 23, 2022, the contents of which are incorporated herein by reference. [Background technology]

[0002] The amino group is a highly reactive functional group that plays an important role in the activity of various organic compounds. In particular, primary amino groups (-NH2) are polar and form hydrogen bonds between molecules and with other molecules, playing an important role in maintaining three-dimensional structures and intermolecular interactions. Because useful organic compounds can be synthesized by aminating organic compounds, various aminating agents have been developed. However, the only amino fluorinating agent that can simultaneously introduce an amino group and a fluorine atom is N-fluorobenzenesulfonimide (NFSI).

[0003] Using imides or sulfonimides protected with a protecting group as an aminofluorinating agent, nitrogen atoms and fluorine atoms can be directly introduced into atoms constituting unsaturated bonds in a substrate by a coupling reaction. An example of a fluorinated sulfonimide used as an aminofluorinating agent is N-fluorobenzenesulfonimide (NFSI). NFSI is used as an aminofluorinating agent in various reactions, such as an aminofluorination reaction in which one carbon atom of a C=C bond of an alkene is aminated and a fluorine atom is introduced into the other carbon atom (Non-Patent Documents 1 and 2), an aminofluorination reaction in which one carbon atom of a saturated bond in a cyclopropane skeleton is aminated and a fluorine atom is introduced into the other carbon atom (Non-Patent Document 3), and an aminofluorination reaction in which an amino group and a fluorine atom are simultaneously introduced into the same carbon atom of a diazocarbonyl compound (Non-Patent Document 4). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2016 / 125845 [Patent Document 2] International Publication No. 2015 / 031725 [Non-patent literature]

[0005] [Non-Patent Document 1] Zhang et al. Angewandte Chemie International Edition, 2014, vol.53, p.11079-11083. [Non-patent document 2] Qiu et al., Journal of the American Chemical Society, 2010, vol.132, p.2856-2857. [Non-patent document 3] Pitts et al., Journal of the American Chemical Society, 2016, vol.138, p.6598-6609. [Non-patent document 4] Chen et al., Chemical Science, 2016, vol.7, p.1786-1790. Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide an amino fluorinating agent capable of introducing an amino group protected with a protecting group that can be deprotected under relatively mild conditions into a wide range of substrates, and a method for producing an amino group- and fluorine-containing compound using the amino fluorinating agent. [Means for solving the problem]

[0007] The present inventors have discovered a compound having a 2-nitrobenzenesulfonyl group (o-nosyl group) and a C 1-30 The present inventors have found that by using a fluorinated sulfonimide compound protected with an alkylsulfonyl group or an optionally substituted phenylsulfonyl group as an amino fluorinating agent, an amino group protected with a protecting group that can be deprotected under relatively mild conditions can be introduced into a wide range of substrates, thereby completing the present invention.

[0008] That is, the present invention is as follows. [1] The following general formula (A)

[0009] [ka]

[0010] [Wherein G is -SO2R 1 , -CO-G 1 , -C(CH3)-Ph; R 1 C may have a halogen atom 1-30 an alkyl group or an optionally substituted phenyl group; G 1 represents an optionally substituted heteroaryl group, or -CG 11 G 12 -G 13 and;G 11 and G 12 are each independently a hydrogen atom, C 1-3 an alkyl group, an alkoxy group, or a fluoroalkyl group; G 13 is an optionally substituted phenyl group; Ph is a phenyl group. A compound represented by the formula: [2] The following general formula (A1)

[0011] [ka]

[0012] [In the formula, R 1 C may have a halogen atom 1-30an alkyl group, or an optionally substituted phenyl group. A compound represented by the formula: [3] R 1 is a methyl group or a 2-nitrophenyl group. [4] An amino fluorinating agent containing any one of the compounds [1] to [3] above as an active ingredient. [5] Using a compound having at least one unsaturated bond as a substrate, the amino fluorinating agent of [4] is used to introduce a fluorine atom into one of the carbon atoms constituting at least one unsaturated bond formed between carbon atoms in the substrate, and to convert the other carbon atom into a compound represented by the following general formula (A1'):

[0013] [ka]

[0014] [In the formula, R 1 C may have a halogen atom 1-30 an alkyl group or an optionally substituted phenyl group.] A method for producing an amino group-containing compound, comprising introducing a group represented by the formula: [6] The substrate is represented by the following general formula (B):

[0015] [ka]

[0016] [In the formula, R 11 and R 21 are each independently a hydrogen atom, a C 1-30 R is an aliphatic hydrocarbon group, an aryl group which may have a substituent, or a heteroaryl group which may have a substituent. 11 and R 21 C 1-30 When the group is an aliphatic hydrocarbon group, these C 1-30 The aliphatic hydrocarbon groups may be linked to each other to form a ring.] The method for producing the amino group-containing compound according to [5] above, which is a compound represented by the formula: [7] R in the general formula (B) 11 and R 21 one of which is a hydrogen atom and the other is a phenyl group which may have a substituent, The substituent is a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 The method for producing an amino group-containing compound according to [6] above, wherein the amino group-containing compound is one or more selected from the group consisting of a fluoroalkyl group, -(C=O)-OCH3, and -O-(C=O)-CH3. [8] The following general formula (B)

[0017] [ka]

[0018] [In the formula, R 11 and R 21 are each independently a hydrogen atom, a C 1-30 R is an aliphatic hydrocarbon group, an aryl group which may have a substituent, or a heteroaryl group which may have a substituent. 11 and R 21 C 1-30 When the group is an aliphatic hydrocarbon group, these C 1-30 The aliphatic hydrocarbon groups may be linked to each other to form a ring.] to a compound represented by the following formula (A1-1):

[0019] [ka]

[0020] is reacted as an amino fluorinating agent, and then a compound represented by the following formula (D-1)

[0021] [ka]

[0022] A method for producing a primary amine by deprotecting the Ns group represented by the formula: [9] The following general formula (B)

[0023] [ka]

[0024] [In the formula, R 11 and R 21 are each independently a hydrogen atom, a C 1-30 R is an aliphatic hydrocarbon group, an aryl group which may have a substituent, or a heteroaryl group which may have a substituent. 11 and R 21 C 1-30 When the group is an aliphatic hydrocarbon group, these C 1-30 The aliphatic hydrocarbon groups may be linked to each other to form a ring.] to a compound represented by the following formula (A1-2):

[0025] [ka]

[0026] is reacted as an amino fluorinating agent, and then a compound represented by the following formula (D-2)

[0027] [ka]

[0028] The Ms group represented by the following formula (D-1) is then deprotected.

[0029] [ka]

[0030] and then deprotecting the Ns group.

[10] The following general formula (A0)

[0031]

Chemical formula

[0032] [In the formula, R 1 is an optionally halogen - atom - bearing C 1-30 alkyl group or an optionally substituted phenyl group, and X is a hydrogen atom or a lithium atom.] Fluorinate the compound represented by the following general formula (A1)

[0033]

Chemical formula

[0034] [In the formula, R 1 is the same as above] to produce a compound represented by the following, a method for producing a compound.

Advantages of the Invention

[0035] The compound according to the present invention can introduce an amino group protected by an o - nosyl group and a C 1-30 alkylsulfonyl group or a phenylsulfonyl group into a wide range of substrates having an unsaturated bond in various reactions similar to NFSI. The amino group protected by these groups can be deprotected under milder conditions than NFSI, so the compound is very useful as an aminofluorinating agent.

Modes for Carrying Out the Invention

[0036] In the present invention and this specification, "C p1-p2 "(p1 and p2 are positive integers satisfying p1 < p2) means a group having a carbon number of p1 to p2.

[0037] In the present invention and this specification, "C 1-30The "alkyl group" is an alkyl group having 1 to 30 carbon atoms, and may be a straight chain or a branched chain. 2-30 The "alkyl group" is an alkyl group having 2 to 30 carbon atoms, and may be either a straight chain or a branched chain. 1-30 Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, neohexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, heneicosyl, docosyl, tricosyl, tetracosyl, pentacosyl, hexacosyl, heptacosyl, octacosyl, nonacosyl, and triacontyl groups.

[0038] In the present invention and the present specification, "C 1-10 The "C alkyl group" is an alkyl group having 1 to 10 carbon atoms, and may be either a straight chain or a branched chain. 2-10 The "alkyl group" is an alkyl group having 2 to 10 carbon atoms, and may be either a straight chain or a branched chain. 1-10 Examples of alkyl groups include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a neopentyl group, a tert-pentyl group, a hexyl group, an isohexyl group, a neohexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group.

[0039] In the present invention and the present specification, "C 1-6 The "alkyl group" is an alkyl group having 1 to 6 carbon atoms, and may be either a straight chain or a branched chain. 1-6Examples of alkyl groups include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a neopentyl group, a tert-pentyl group, a hexyl group, an isohexyl group, and a neohexyl group.

[0040] In the present invention and the present specification, "C 1-3 The "alkyl group" is an alkyl group having 1 to 3 carbon atoms, and may be either a straight chain or a branched chain. 1-3 Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, and an isopropyl group.

[0041] In the present invention and the present specification, "C having a substituent" p1-p2 "Alkyl group" is C p1-p2 It is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to a carbon atom of an alkyl group are substituted with other functional groups. When the alkyl group has two or more substituents, the substituents may be the same or different. The substituents include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, or iodine atoms), optionally substituted C 6-14 Examples include an aryl group, a cyano group, and a nitro group.

[0042] "C having a substituent p1-p2 Examples of "alkyl groups" include C 6-14 Aryl-C 1-6 Examples of alkyl groups include "C 6-14 Aryl-C 1-6 "Alkyl group" is C 1-6 One hydrogen atom attached to a carbon atom of an alkyl group is C 6-14 It is a group substituted with an aryl group. 6-14 Aryl-C 1-6 C in alkyl groups 6-14 Examples of the aryl group include a phenyl group, a naphthyl group, an anthryl group, and a 9-fluorenyl group, with a phenyl group or a 9-fluorenyl group being particularly preferred. 6-14 Aryl-C 1-6 C in alkyl groups1-6 The alkyl group is C 1-4 Alkyl groups are preferred. 6-14 Aryl-C 1-6 Examples of the alkyl group include a benzyl group, a diphenylmethyl group, a triphenylmethyl group, a 2-phenylethyl group, a 9-anthrylmethyl group, and a 9-fluorenylmethyl group.

[0043] In the present invention and the present specification, "C 1-30 The "aliphatic hydrocarbon group" is a C 1-30 alkyl group, optionally substituted C 2-30 Alkenyl group, optionally substituted C 2-30 Alkynyl groups, including all of the above. 1-30 The "aliphatic hydrocarbon group" may be a straight chain, a branched chain, or a cyclic group. 2-30 Examples of alkenyl groups include C 2-30 Among the alkyl groups mentioned above, groups in which at least one single bond between carbon atoms is converted into a double bond are exemplified. 2-30 Examples of alkynyl groups include C 2-30 Among the alkyl groups mentioned above, groups in which at least one single bond between carbon atoms is converted into a triple bond are exemplified. More specifically, C 2-30 Examples of the alkenyl group include a vinyl group, a propenyl group, a 2-propenyl group, a butenyl group, a 1-methylpropenyl group, a 2-methylpropenyl group, a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, a nonenyl group, a decenyl group, a cyclobutenyl group, a cyclopentenyl group, and a cyclohexenyl group. 2-30 Examples of the alkynyl group include an ethynyl group, a propynyl group, a butynyl group, a 1-methylpropynyl group, a pentynyl group, a 2-methylbutynyl group, a hexynyl group, a heptynyl group, and an octynyl group.

[0044] In the present invention and the present specification, "C having a substituent" p1-p2 Aliphatic hydrocarbon group" is C p1-p2It is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to carbon atoms of an aliphatic hydrocarbon group are substituted with other functional groups. When the group has two or more substituents, the substituents may be the same or different from each other. The substituents include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, or iodine atoms), optionally substituted C 6-14 Examples include an aryl group, a cyano group, and a nitro group.

[0045] In the present invention and the present specification, "C 1-30 The term "alkoxy group" refers to a group in which an oxygen atom is bonded to the bond terminal of a linear or branched alkyl group having 1 to 30 carbon atoms. 1-30 The term "alkylthio group" refers to a group in which a sulfur atom is bonded to the bond terminal of a linear or branched alkyl group having 1 to 30 carbon atoms. 1-30 Alkoxy group or C 1-30 The linear or branched alkyl group having 1 to 30 carbon atoms in the alkylthio group includes the above-mentioned C 1-30 The same as the alkyl group can be mentioned.

[0046] In the present invention and the present specification, "C 1-10 The term "alkoxy group" refers to a group in which an oxygen atom is bonded to the bond terminal of a linear or branched alkyl group having 1 to 10 carbon atoms. 1-10 The term "alkylthio group" refers to a group in which a sulfur atom is bonded to the bond terminal of a linear or branched alkyl group having 1 to 10 carbon atoms. 1-10 Alkoxy group or C 1-10 The linear or branched alkyl group having 1 to 10 carbon atoms in the alkylthio group includes the above-mentioned C 1-10 The same as the alkyl group can be mentioned.

[0047] In the present invention and the present specification, "C 1-6 The term "alkoxy group" refers to a group in which an oxygen atom is bonded to the bond terminal of a linear or branched alkyl group having 1 to 6 carbon atoms. 1-6The term "alkylthio group" refers to a group in which a sulfur atom is bonded to the bond terminal of a linear or branched alkyl group having 1 to 6 carbon atoms. 1-6 Alkoxy group or C 1-6 The linear or branched alkyl group having 1 to 6 carbon atoms in the alkylthio group includes the above-mentioned C 1-6 The same as alkyl groups can be used. 1-6 Examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a tert-butoxy group, a pentyloxy group, and a hexyloxy group. 1-6 Examples of the alkylthio group include a methylthio group, an ethylthio group, a propylthio group, a butylthio group, a tert-butylthio group, a pentylthio group, and a hexylthio group.

[0048] In the present invention and the present specification, "C having a substituent" p1-p2 The "alkoxy group" is C p1-p2 In the present invention and this specification, "substituted C" refers to a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to a carbon atom of an alkoxy group are substituted with other functional groups. p1-p2 The alkylthio group is C p1-p2 It is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to the carbon atom of the alkylthio group are substituted with other functional groups. When the alkylthio group has two or more substituents, the substituents may be the same or different. The substituents include halogen atoms (fluorine atoms, chlorine atoms, bromine atoms, or iodine atoms), optionally substituted C 6-14 Examples include an aryl group, a cyano group, and a nitro group.

[0049] In the present invention and the present specification, "C 6-14 The "aryl group" is an aromatic hydrocarbon group having 6 to 14 carbon atoms, 6-12 An aryl group is particularly preferred. 6-14 Examples of the aryl group include a phenyl group (C6 aryl group), a naphthyl group, an anthryl group, and a 9-fluorenyl group, with a phenyl group being particularly preferred.

[0050] In the present invention and the present specification, "optionally substituted C 6-14 The "aryl group" is C 6-14 It is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to carbon atoms of the aryl group are substituted with other functional groups. When the aryl group has two or more substituents, the substituents may be the same or different from each other. The substituents include C 1-6 Alkyl group, C 1-6 Examples of the substituted or unsubstituted C include an alkoxy group, a methylenedioxy group (-O-CH2-O-), a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), and a nitro group. 6-14 Examples of the "aryl group" include a phenyl group, a naphthyl group, an anthryl group, a 4-methylphenyl group, a 2,6-dimethylphenyl group, a 4-methoxyphenyl group, a 2,4-dimethoxyphenyl group, a 3,4-dimethoxyphenyl group, a 3-chlorophenyl group, a 2-nitrophenyl group, a 3-nitrophenyl group, a 4-nitrophenyl group, and a 1,3-benzodioxol-5-yl group.

[0051] In the present invention and this specification, a "heteroaryl group" refers to a cyclic group having aromaticity, and the ring is composed of carbon atoms and atoms other than carbon atoms. The heteroaryl group may be a group containing a nitrogen atom (nitrogen-containing heteroaryl group), a group containing an oxygen atom (oxygen-containing heteroaryl group), or a group containing a sulfur atom (sulfur-containing heteroaryl group). In addition, the aromatic ring may contain two or more types of atoms other than carbon atoms.

[0052] C 5-14 Examples of nitrogen-containing heteroaryl groups include pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, benzimidazolyl, benzotriazolyl, quinolyl, isoquinolyl, quinazolyl, and carbazolyl groups. 5-14Examples of oxygen-containing heteroaryl groups include furanyl, pyranyl, benzopyranyl, and xanthenyl groups. 5-14 Examples of sulfur-containing heteroaryl groups include thienyl groups. 5-14 Examples of the heteroaryl group include an oxazolyl group, an isoxazolyl group, a thiazolyl group, and an isothiazolyl group.

[0053] In the present invention and the present specification, a "substituted heteroaryl group" refers to a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to atoms constituting the aromatic ring of the heteroaryl group are substituted with other functional groups. When the heteroaryl group has two or more substituents, the substituents may be the same or different from each other. Examples of the substituents include C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Examples include an alkylthio group, a methylenedioxy group (-O-CH2-O-), a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), a trihalomethyl group, a cyano group, and a nitro group.

[0054] In the present invention and this specification, the term "aromatic group" includes both an aryl group (aromatic hydrocarbon group) which may have a substituent and a heteroaryl group (heterocyclic group) which may have a substituent.

[0055] In the following description, "compound (n)" means a compound represented by formula (n).

[0056] Subsequent chemical reactions can be carried out in an inert solvent such as methanol, 1,4-dioxane, diethyl ether, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), dichloromethane (DCM), dichloroethane (DCE), acetonitrile (MeCN), triethylamine (TEA), benzene, toluene, N,N-dimethylformamide (DMF), or N,N-dimethylacetamide.

[0057] [Amino fluorinating agents] The compound according to the present invention is a compound represented by the following general formula (A): In general formula (A), G is -SO2R 1 , -CO-G 1 , -C(CH3)-Ph, where Ph is a phenyl group.

[0058] [ka]

[0059] In general formula (A), R 1 C may have a halogen atom 1-30 R is an alkyl group or an optionally substituted phenyl group. 1 Specifically, R in general formula (A1) described below is 1 The same groups as those shown in the formula (I) can be used.

[0060] In general formula (A), G 1 represents an optionally substituted heteroaryl group, or -CG 11 G 12 -G 13 G 11 and G 12 are each independently a hydrogen atom, C 1-3 is an alkyl group, an alkoxy group, or a fluoroalkyl group, and G 13 is a phenyl group which may have a substituent.

[0061] G 1 When C is an optionally substituted heteroaryl group, the heteroaryl group is preferably a nitrogen-containing heteroaryl group, and 5-14 A nitrogen-containing heteroaryl group is more preferred, and a pyridyl group is even more preferred.

[0062] G 11 and G 12 When is an alkoxy group, the alkoxy group is C 1-6An alkoxy group is preferred, a methoxy group, an ethoxy group, or a propoxy group is more preferred, and a methoxy group is even more preferred. 11 and G 12 When is a fluoroalkyl group, the fluoroalkyl group may be C 1-6 A group in which one or more hydrogen atoms of an alkyl group are substituted with a fluorine atom is preferred, and C 1-3 A group in which one or more hydrogen atoms of an alkyl group have been substituted with a fluorine atom is more preferred, a group in which one or more hydrogen atoms of a methyl group have been substituted with a fluorine atom is even more preferred, and a trifluoromethyl group is particularly preferred.

[0063] A phenyl group having a substituent is a group in which one or more, preferably 1 to 3, of the hydrogen atoms bonded to the carbon atoms of the phenyl group have been substituted with other functional groups. When the phenyl group has two or more substituents, the substituents may be the same or different. G 13 As the phenyl group or C 1-6 Alkyl group, C 1-6 A phenyl group having one or more substituents selected from the group consisting of an alkoxy group, a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), and a nitro group is preferred, and a phenyl group or a C 1-6 A phenyl group substituted with an alkyl group is more preferred.

[0064] G in general formula (A) 1 Ga-CG 11 G 12 -G 13 If -CG 11 G 12 -G 13 As for G 11 and G 12 are each independently a hydrogen atom, a methyl group, a trifluoromethyl group, or a methoxy group, and G 13 is preferably a phenyl group substituted with an alkyl group, and G 11 and G 12 are each independently a hydrogen atom, a methyl group, a trifluoromethyl group, or a methoxy group, and G 13 C 1-6A group that is a phenyl group substituted with an alkyl group is more preferred, and G 11 and G 12 are each independently a hydrogen atom, a methyl group, a trifluoromethyl group, or a methoxy group, and G 13 is a methylphenyl group is more preferred.

[0065] The compound according to the present invention is preferably a compound represented by the following general formula (A1): 1 C may have a halogen atom 1-30 It is an alkyl group or a phenyl group which may have a substituent.

[0066] [ka]

[0067] R 1 C which may have a halogen atom 1-30 When the R 1 C which may have a halogen atom 1-6 Alkyl groups are preferred, and unsubstituted C 1-6 C having an alkyl group, a fluorine atom, or a chlorine atom as a substituent 1-6 Alkyl groups are more preferred, and unsubstituted C 1-6 Alkyl groups are more preferred, with methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, and neohexyl groups being even more preferred, and methyl groups being particularly preferred.

[0068] R 1 is a phenyl group which may have a substituent, the compound (A1) may be 1 is preferably a phenyl group which may have a substituent, and C 1-6 Alkyl group, C 1-6A phenyl group optionally having one or more substituents selected from the group consisting of an alkoxy group, a halogen atom, and a nitro group is more preferred, a phenyl group optionally having one or more substituents selected from the group consisting of a fluorine atom, a chlorine atom, and a nitro group is even more preferred, a nitrophenyl group is even more preferred, and an o-nitrophenyl group is particularly preferred.

[0069] Compound (A1) can be synthesized, for example, by synthesizing a sulfonimide by the condensation reaction of a sulfonyl halide with a sulfonamide, substituting a hydrogen atom bonded to a nitrogen atom of the imide group with a lithium atom, and then substituting the lithium atom with a fluorine atom. 1 is R in general formula (A1) 1 is the same as

[0070] [ka]

[0071] Although the above reaction is an example in which a lithium atom is used, the same reaction is possible even if the lithium atom is replaced with another alkali metal atom such as a sodium atom or a potassium atom. Furthermore, in the above reaction, it is also possible to directly substitute a hydrogen atom with a fluorine atom without substituting the hydrogen atom with a lithium atom.

[0072] That is, the compound (A1) can be produced by fluorinating a compound represented by the following general formula (A0): 1 is R in general formula (A1) 1 and X is a hydrogen atom or a lithium atom.

[0073] [ka]

[0074] Compound (A) other than compound (A1) can be produced by first synthesizing compound (8) as described below, and then reacting compound (8) with a sulfonyl compound, an acid chloride compound, a carboxylic acid group-containing compound, a hydroxy group-containing compound, or the like.

[0075] [ka]

[0076] [Method of producing amino fluorinating agent] Compound (A1) can be used as an active ingredient of an amino fluorinating agent in various reactions. Compound (A1), like NFSI, can amine carbon atoms in various organic compounds. Examples of organic compounds that can serve as substrates include compounds with unsaturated bonds, such as alkenes, allylic compounds, alkynes, and aromatic compounds. The unsaturated bond may be a bond formed between carbon atoms, or may be a bond between a carbon atom and an atom other than a carbon atom. Compound (A1) can also use organic compounds containing a tricyclo ring as substrates.

[0077] For example, a compound having at least one unsaturated bond can be used as a substrate, and compound (A1) can be used as an amino fluorinating agent to introduce a group represented by the following general formula (A1') into one of the carbon atoms constituting at least one unsaturated bond in the substrate. At that time, a fluorine atom is introduced into the other carbon atom constituting the unsaturated bond. In general formula (A1'), R 1 is R in general formula (A1) 1 The black circle represents a bond. In the following chemical formulas, the group represented by general formula (A1') may be represented as "-[N]". By introducing the group represented by general formula (A1'), an amino group-containing compound can be produced.

[0078] [ka]

[0079] <1,2-Amino Fluorination Reaction> When an alkene is used as a substrate compound, the group represented by the general formula (A1') can be introduced into at least one of the two carbon atoms constituting the unsaturated bond in the alkene. For example, by the following 1,2-aminofluorination reaction, the group represented by the general formula (A1') can be introduced into one of the two carbon atoms constituting the C=C bond in the alkene to amminate it, and a fluorine atom can be introduced into the other carbon atom.

[0080] [ka]

[0081] As the alkene that serves as the substrate compound for the 1,2-aminofluorination reaction, for example, compound (B) can be used. In general formula (B), R 11 and R 21 are each independently a hydrogen atom, a C 1-30 It is an aliphatic hydrocarbon group, an aryl group which may have a substituent, or a heteroaryl group which may have a substituent. 11 and R 21 C 1-30 When the group is an aliphatic hydrocarbon group, these C 1-30 The aliphatic hydrocarbon groups may be linked to each other to form a ring. 1-30 The substituents on the aliphatic hydrocarbon group, aryl group, and heteroaryl group are not particularly limited as long as they do not inhibit the 1,2-aminofluorination reaction of the C=C bond by compound (A1).

[0082] A compound obtained by introducing a group represented by general formula (A1') into one of the two carbon atoms constituting the C=C bond in an alkene to fluorinate it and introducing a fluorine atom into the other carbon atom to fluorinate it can be obtained by carrying out a 1,2-aminofluorination reaction using an alkene substrate and compound (A1) in the presence of a catalyst such as a Pd catalyst. The reaction conditions for the 1,2-aminofluorination reaction can be similar to those for the 1,2-aminofluorination reaction using NFSI described in Example 3 below, Non-Patent Document 2, Non-Patent Document 6, etc., or under conditions with appropriate modifications of these.

[0083] [Method for producing primary or secondary amines using deprotection reaction of amino group] The compound having the group represented by general formula (A1') introduced therein can be converted into a primary amino group by a deprotection reaction utilizing a nucleophilic addition reaction to a carbonyl group, thereby producing an amino group-containing compound having a primary amino group introduced into one of the two carbon atoms that constituted the unsaturated bond aminated by compound (A1).

[0084] Compounds aminated with NFSI require very harsh reaction conditions, such as refluxing in the presence of elemental metals like magnesium or strong acids like trifluoromethanesulfonic acid (TfOH) or sulfuric acid. In contrast, the deprotection reaction of compounds aminated with compound (A1) involves a nucleophilic addition reaction to the o-nosyl group represented by general formula (A1'). This allows the deprotection reaction to be carried out under relatively mild conditions, without the need for elemental metals or strong acids.

[0085] [Method of producing primary amines] General formula (A1')(R 1 By reacting the group represented by (=-o-NO2C6H4) with potassium carbonate and benzenethiol, deprotection proceeds at room temperature, and it can be converted into a primary amino group.

[0086] For example, when compound (B) is used as a substrate, a primary amine can be produced by reacting compound (B) with compound (A1-1) as an amino fluorinating agent, and then deprotecting the Ns group represented by the following formula (D-1).

[0087] [ka]

[0088] [ka]

[0089] [Method of producing secondary amines] In the first deprotection step, a compound of formula (A1') (R 1 By applying LDA to a group represented by the formula (=-CH3) under 1 atmosphere of oxygen, a derivative with the -NH-SO2-(o-NO2C6H4) structure can be synthesized. In the second nucleophilic substitution reaction, by applying an alcohol (ROH) under Mitsunobu reaction conditions, a derivative with the corresponding -NR-SO2-(o-NO2C6H4) structure can be synthesized. In the third deprotection step, deprotection proceeds at room temperature by applying potassium carbonate and benzenethiol, synthesizing a derivative with the secondary amino group -NHR structure.

[0090] For example, when compound (B) is used as a substrate, compound (A1-2) is reacted with compound (B) as an amino fluorinating agent, and then the Ms group represented by the following formula (D-2) is deprotected. Thereafter, the nitrogen atom to which the remaining Ns group is bonded is alkylated, and the Ns group is then deprotected, thereby producing a secondary amine.

[0091] [ka]

[0092] [ka] [Example]

[0093] The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[0094] <nmr> The spectrophotometer used for the NMR spectrum analysis in the examples and comparative examples was a JNM-ECZ400S ( 1 H: 400MHz, 13 C: 100MHz, 19 F:376MHz) or JEOL JNM-ECZ500R ( 1 H: 500MHz, 13 C: 125MHz, 19 F:470MHz). 1 H NMR chemical shifts were determined relative to the internal (CH3)4Si(TMS) δ = 0.0 ppm or to the signals of residual protonated solvents (CDCl3 δ = 7.26 ppm; acetone-d6 δ = 2.05 ppm; DMSO-d6 δ = 2.50 ppm). 13 C NMR chemical shifts were determined relative to internal TMS δ = 0.0 ppm or to the signals of residual protonated solvent (CDCl δ = 77.16 ppm; acetone-d δ = 29.84, 206.26 ppm). 19 F NMR chemical shifts were determined relative to CFCl δ = 0.0 ppm. 1 H, 13 C, and 19 F NMR data were reported as chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, q = quartet, br = broad). IR spectra were measured on a Shimadzu FTIR-8400 spectrometer, and high-resolution mass spectrometry (HRMS) spectra were measured on a JEOL JMS-T100LP spectrometer in electrospray ionization time-of-flight (ESI-TOF) mode. The yields (%) shown in the examples are in mole %.

[0095] In the following examples, all reactions were carried out using commercially available reagents and solvents. All reagents and starting materials were purchased from Sigma-Aldrich, Kanto Chemical, TCI, and / or Fujifilm Wako Pure Chemical Industries, Ltd. and used without further purification. All solvents were purchased from Sigma-Aldrich, Kanto Chemical, TCI, and / or Fujifilm Wako Pure Chemical Industries, Ltd. and used without further purification unless otherwise specified.

[0096] [Example 1] The sulfonimide was synthesized according to the following synthetic procedure.

[0097] [ka]

[0098] A solution of sulfonamide (1.2 equiv.) in THF (0.1 M) was added to NaH (2.2 equiv.) at 0° C. and stirred at room temperature under nitrogen atmosphere for 1 hour. Sulfonyl chloride was added to the solution at 0° C. and stirred at reflux for an additional 48 hours at 80° C. After completion of the reaction, the reaction was quenched (1 M HCl) and extracted twice with DCM. The combined organic extracts were washed (brine), dried (NaSO), and concentrated in vacuo. The resulting crude product was purified by silica gel column chromatography to give sulfonimide 1.

[0099] (1) Synthesis of N-(2,2'-dinitro)benzenesulfonimide N-(2,2'-dinitro)benzenesulfonimide was obtained from 2-nitrobenzenesulfonamide (7.2 mmol) according to the procedure described above. Purification by silica gel column chromatography (DCM / MeOH = 1 / 0 to 10 / 1 (volume ratio)) afforded N-(2,2'-dinitro)benzenesulfonimide (1.99 g, 69% yield) as an orange solid.

[0100] [ka]

[0101] 1 H NMR (500 MHz, (CD3)2CO) δ 8.24(d, J = 7.5 Hz, 2H), 7.99(d, J = 4.5 Hz, 4H), 7.94(m, 2H). 13 C NMR (125 MHz, (CD3)2CO) δ 147.97(s, 2C), 135.61(s, 2C), 132.85(s, 2C), 132.65(s, 2C), 131.74(s, 2C), 125.10(s, 2C).

[0102] (2) Synthesis of N-(2-nitrobenzenesulfonyl)methanesulfonamide According to the procedure described above, N-(2-nitrobenzenesulfonyl)methanesulfonamide was obtained from methanesulfonamide (10.0 mmol). Purification by silica gel column chromatography (DCM / MeOH = 1 / 0 to 10 / 1 (volume ratio)) gave N-(2-nitrobenzenesulfonyl)methanesulfonamide (1.87 g, 67% yield) as a brown solid.

[0103] [ka]

[0104] 1 H NMR (500 MHz, CDCl3) δ 8.27(d, J = 7.5 Hz, 1H), 7.96-8.05(m, 3H), 3.40(s, 3H). 13 C NMR (125 MHz, CDCl3) δ 147.97(s), 135.51(s), 132.80(s, 2C), 131.95(s), 125.09(s), 43.42(s).

[0105] [Example 2] The amino fluorinating agent was synthesized according to the following synthesis procedure.

[0106] [ka]

[0107] Sulfonimide and lithium hydroxide monohydrate were added to acetone solvent (100 mL) and stirred at room temperature for 1 hour. The solvent was then distilled off under vacuum to obtain the lithium salt of sulfonimide as a white solid. Next, a solution of the lithium salt of sulfonimide was added to a mixed solvent of 95 wt% acetonitrile / water (180-200 mL), stirred, and then cooled to 0°C. A gas mixture of nitrogen gas and 2% fluorine gas (volume percent) was introduced into the solution at a rate of 100 mL / min. The insoluble solid was filtered, and the filtrate was evaporated under vacuum to obtain a yellow solid. The crude product was purified by washing with hexane to obtain the target compound as a white solid.

[0108] (1) Synthesis of N-fluoro-N-(2,2'-dinitro)benzenesulfonimide Following the procedure described above, N-fluoro-N-(2,2'-dinitro)benzenesulfonimide was obtained from sulfonimide (8.27 mmol), which was purified by washing with hexane to give N-fluoro-N-(2,2'-dinitro)benzenesulfonimide (3.05 g, 91% yield) as a white solid.

[0109] [ka]

[0110] 1 H NMR (500 MHz, CDCl3) δ 8.37 (d, J = 8.59 Hz, 2H), 8.26 (t, J = 7.73 Hz, 2H), 8.17-8.10 (m, 4H). 13 C NMR (125 MHz, CDCl3) δ 148.95 (s, 2C), 138.76(s, 2C), 133.20(s, 2C), 133.18(s, 2C), 126.61(s, 2C), 125.58(s, 2C). 19 F NMR (470 MHz, CDCl3) δ -35.64 (s).

[0111] (2) Synthesis of N-fluoro-N-(2-nitrobenzenesulfonyl)methanesulfonamide Following the procedure described above, N-fluoro-N-(2-nitrobenzenesulfonyl)methanesulfonamide was obtained from sulfonimide (6.7 mmol) and purified by washing with hexane to give N-fluoro-N-(2-nitrobenzenesulfonyl)methanesulfonamide (1.96 g, 99% yield) as a white solid.

[0112] [ka]

[0113] 1 H NMR (500 MHz, CDCl3) δ 8.37 (dd, J = 1.15, 9.16, 1H), 8.24 (dt, J = 8.31, 1.15, 1H), 8.15(dd, J = 9.16, 1.15, 1H), 8.10 (dt, J = 16.6, 1.15, 1H), 3.67 (d, J = 1.72, 3H). 13 C NMR (125 MHz, CDCl3) δ 148.78(s), 139.36(s), 134.03(s), 133.90(s), 127.38(s), 126.33(s), 40.93(s). 19 F NMR (470 MHz, CDCl3) δ -40.84 (s).

[0114] [Example 3] An amino fluorinating agent was synthesized from N-fluoro-N-2-nitrobenzenesulfonamide.

[0115] (1) Synthesis of N-fluoro-N-2-nitrobenzenesulfonamide N-fluoro-N-2-nitrobenzenesulfonamide was synthesized as a novel precursor of NF reagents.

[0116] [ka]

[0117] The lithium salt was synthesized in the same manner as in Example 2. The synthesized lithium salt solution of sulfonimide was added to a mixed solvent of 95 wt% acetonitrile / water (180-200 mL), stirred, and then cooled to 0°C. A gas mixture of nitrogen gas and 2% fluorine gas (volume percent) was introduced into the solution at a rate of 100 mL / min. The insoluble solid was filtered, and the filtrate was evaporated under vacuum to obtain a yellow solid as the crude product of N-fluoro-N-2-nitrobenzenesulfonamide (compound (8)). The crude product was added to dichloromethane (0.05 M), 200% by mass of silica gel was added, and the mixture was stirred at room temperature for 1 day.

[0118] 1 H NMR (500 MHz, CDCl3) δ 9.82 (d, J = 52.12, 1H), 8.32 (dd, J = 1.15, 9.16, 1H), 8.00 (dd, J = 1.15, 9.16, 1H), 7.94 (dt, J = 1.15, 9.16, 1H), 7.89 (dt, J = 1.15, 9.16, 1H). 13 C NMR (125 MHz, CDCl3) δ 148.69, 136.29, 134.56, 133.65, 128.52, 126.25. 19 F NMR (470 MHz, CDCl3) δ -91.26 (d, J = 50.38).

[0119] (2) Synthesis of N-fluoro-N-(2-nitrobenzenesulfonyl)benzenesulfonamide

[0120] [ka]

[0121] Compound (8) (44.0 mg, 0.2 mmol), lutidine (27.9 μL, 0.24 mmol), benzenesulfonyl chloride (30.6 μL, 0.24 mmol), and DCM (1 mL) were added to a dry glass tube. The resulting reaction mixture was stirred at 0° C. for 9 hours and then purified directly by silica gel column chromatography (hexane / DCM = 1 / 1 (volume ratio)).

[0122] 1 H NMR (400 MHz, CDCl3) δ 8.22(d, J = 8.02, 1H), 8.09(dd, J = 1.15, 8.59, 2H), 7.92(td, J = 1.15, 7.73, 1H), 7.82(dd, J = 7.45, 3H), 7.65(dd, J = 1.15, 8.02, 2H). 13 C NMR (125 MHz, CDCl3) δ 148.94, 136.97, 136.43, 134.61, 132.95, 132.45, 130.19, 129.78, 128.35, 125.71. 19 F NMR (470 MHz, CDCl3) δ -34.42.

[0123] (3) Synthesis of N-fluoro-N-(2-nitrobenzenesulfonyl)ethanesulfonamide

[0124] [ka]

[0125] Compound 8 (44.0 mg, 0.2 mmol), lutidine (27.9 μL, 0.24 mmol), ethanesulfonyl chloride (19.9 μL, 0.24 mmol), DMAP (4.9 mg, 0.04 mmol), and DCM (1 mL) were added to a dry glass tube, and the reaction mixture was stirred at 0° C. for 9 h.

[0126] 19 F NMR (376 MHz, CDCl3) δ -39.08(s).

[0127] (4) Synthesis of N-fluoro-N-(2-nitrobenzenesulfonyl)pyridineamide

[0128] [ka]

[0129] Compound 8 (44.0 mg, 0.2 mmol), lutidine (51.1 μL, 0.44 mmol), 2-pyridine acid chloride (42.7 mg, 0.24 mmol), and DCM (1 mL) were added to a dry glass tube, and the resulting reaction mixture was stirred at 0° C. for 6 hours.

[0130] 19 F NMR (376 MHz, CDCl3) δ -55.04.

[0131] (5) Synthesis of (R)-N,3,3,3-tetrafluoro-2-methoxy-N-((2-nitrophenyl)sulfonyl)-2-phenylpropanamide

[0132] [ka]

[0133] In a dry glass tube, compound 8 (22.0 mg, 0.1 mmol), pyridine (9.7 μL, 0.12 mmol), acid chloride (22.5 μL, 0.12 mmol), and DCM (1 mL) were added, and the reaction mixture was stirred at room temperature for 3 hours.

[0134] 19 F NMR (470 MHz, CDCl3) δ -47.206(s, 1F), -71.23(s, 3F).

[0135] (6) Synthesis of (S)-N-fluoro-2-(4-isobutylphenyl)-N-((2-nitrophenyl)sulfonyl)propenamide

[0136] [ka]

[0137] Compound (8) (44.0 mg, 0.2 mmol), carboxylic acid (43.3 mg, 0.21 mmol), lutidine (43.3 μL), and ethyl acetate (86.6 μL) were added to a dry glass tube, followed by the addition of a 1.7 M solution of T3P in ethyl acetate (247.1 μL, 0.42 mmol) at -20 °C and stirring at 0 °C for 24 h. The reaction was quenched with water, separated with DCM, and the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (DCM 100%).

[0138] 1 H NMR (500 MHz, CDCl3) δ 8.19(dd, J = 1.15, 7.73, 1H), 7.86(ddd, J = 1.15, 7.73, 1H),7.78-7.74(m, 2H), 7.10(d, J = 8.02, 2H), 7.04(d, J = 8.02, 2H), 4.24(qd, J = 7.16, 2.86, 1H), 2.42(d, 6.87, 2H), 1.82(m, J = 6.87, 1H), 1.51(d, J = 6.87, 3H), 0,89(d, J = 6.87, 6H). 13 C NMR (125 MHz, CDCl3) δ 173.44, 148.33, 141.45, 136.36, 134.92, 134.21, 132.43, 129.75, 128.51, 127.59, 125.01, 45.20, 30.26, 22.46, 22.41, 18.56. 19 F NMR (471 MHz, CDCl3) δ -49.06.

[0139] (7) Synthesis of (S)-N-fluoro-2-nitro-N-(1-phenylethyl)benzenesulfonamide

[0140] [ka]

[0141] Compound (8) (44.0 mg, 0.2 mmol), triphenylphosphine (68.2 mg, 0.26 mmol), alcohol (31.4 μL, 0.26 mmol), and DCM (1 mL) were added to a dry glass tube, followed by a THF solution of DIAD (1.9 M, 0.26 mmol) with stirring at 0 °C. The resulting reaction mixture was stirred at room temperature for 9 hours, and the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (hexane / DCM = 1 / 4 (volume ratio)).

[0142] 1 H NMR (400 MHz, CDCl3) δ 8.13(dd, J = 8.00, 0.91), 7.83-7.69(m, 3H), 7.48-7.28(m, 5H), 5.30-5.19(m, 1H), 1.79(dd, J = 6.86, 0.91, 3H). 19 F NMR (376 MHz, CDCl3) δ-70.87(d, J = 34.68).

[0143] [Example 4] The aminofluorination reaction was carried out using the aminofluorinating agent synthesized in Example 2.

[0144] [ka]

[0145] (1) Synthesis of N-[2-fluoro-1-(4-fluorophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-2-nitrobenzenesulfonamide (3a) In a dry glass tube, Pd(OAc)2 (2.3 mg, 0.01 mmol, 5 mol%), bathocuproine (BC) (5.4 mg, 0.015 mmol, 7.5 mol%), and the aminofluorinating agent compound (1a) (0.3 mmol, 1.5 equiv.) synthesized in Example 2 were dissolved in 1,4-dioxane (1.0 mL), followed by the addition of fluorinated styrene (0.2 mmol, 1.0 equiv.). The reaction mixture was stirred at 50 °C for 1 to 2.5 h, after which the solvent was removed under vacuum. The residue containing the aminofluorinated product was purified by silica gel column chromatography (DCM / hexane = 1 / 1 (v / v)) to obtain N-[2-fluoro-1-(4-fluorophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-2-nitrobenzenesulfonamide (compound (3a)) (85.5 mg, 81% yield) as a white solid.

[0146] [ka]

[0147] 1 H NMR (500 MHz, CDCl3) δ 7.84-7.53(m, 10H), 6.99(dd, J = 8.59, 2H), 6.04(ddd, J = 7.45, 12.03), 5.32(ddd, J = 9.45, 7.45, 45.97, 1H), 5.05(ddd, J = 6.87, 9.74, 46.39). 13 C NMR (125 MHz, CDCl3) δ163.32(d, J = 251.09), 148.37, 134.99, 132.78, 132.20, 131.99(d, J = 8.45), 131.28, 128.30, 124.28, 116.13(d, J = 20.52), 82.09(d, J = 175.04), 63.83(d, J = 26.56). 19 F NMR (470 MHz, CDCl3) δ -110.32(s), -216.14(dt, J = 14.40, 43.19).

[0148] (2) Synthesis of N-[2-fluoro-1-(4-fluorophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide (3b) The aminofluorination reaction was carried out in the same manner as in (1) above, except that compound (1b) was used instead of compound (1a) as the aminofluorinating agent, and the solvent was removed to obtain a residue containing an aminofluorinated product. The obtained residue was purified by silica gel column chromatography (DCM / hexane = 1 / 1 (volume ratio)) to obtain N-[2-fluoro-1-(4-fluorophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide (78.4 mg, yield 89%) as a white solid.

[0149] [ka]

[0150] 1 H NMR (500 MHz, CDCl3) δ8.18(s, 1H), 7.74-7.56(m, 5H), 7.09(dd, J = 8.02), 5.98(td, J = 6.87, 1H), 5.23(q, 2H), 2.91(s, 3H). 13 C NMR (125 MHz, CDCl3) δ 163.15(d, J = 249.89), 148.18, 133.19(2C), 132.26, 131.38(d, J = 7.24, 2C), 128.59, 124.41, 124.25, 116.26(d, J = 21.73, 2C), 82.47(d, J = 172.63), 62.34, 45.01. 19 F NMR (470 MHz, CDCl3) δ -110.68(s), -216.06(br).

[0151] (3) Synthesis of tert-butyl [2-fluoro-1-(4-fluorophenyl)ethyl]carbamate (4a)

[0152] [ka]

[0153] Compound (3a) (52.7 mg, 0.1 mmol), potassium carbonate (82.9 mg, 0.6 mmol), benzenethiol (40.8 μL, 0.4 mmol), and acetonitrile (2 mL) were added to a dry glass tube. The reaction mixture was stirred at room temperature for 3 hours, and then the solvent was removed under vacuum. To the residue, Boc(tert-butoxycarbonyl) anhydride (32.7 mg, 0.15 mmol), TEA (13.9 μL, 0.1 mmol), and DCM (2 mL) were added. The reaction mixture was stirred at 0°C for 24 hours, and then the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (hexane / DCM = 3 / 1 to 1 / 1 (volume ratio)).

[0154] In addition, 2-fluoro-1-(4-fluorophenyl)ethanamine 19 F NMR measurement confirmed that the compound was produced as an intermediate.

[0155] 19 F NMR (376 MHz, CDCl3) δ -115.04(s), -219.54(s)

[0156] tert-Butyl [2-fluoro-1-(4-fluorophenyl)ethyl]carbamate (4a): 1 H NMR (500 MHz, CDCl3) δ 7.30(dd,J = 5.49, 3.20, 2H), 7.04(dd, J = 8.69, 2H), 5.15(s, 1H), 4.90(d, J = 21.96),4.70-4.49(m, 2H), 1.43(s, 9H). 13 C NMR (125 MHz, CDCl3) δ162.50(d, J = 247.47), 156.24, 134.36, 128.62(d, J = 8.45, 2C), 115.77(d, J = 21.73, 2C), 85.19(d, J = 176.25), 80.33, 54.12, 28.44(3C). 19 F NMR (470 MHz, CDCl3) δ -114.36(s), -226.66(d, J = 21.59).

[0157] (4) Synthesis of N-[2-fluoro-1-(4-fluorophenyl)ethyl]-2-nitrobenzenesulfonamide (5b)

[0158] [ka]

[0159] Compound (3b) (44.0 mg, 0.1 mmol) and THF (1 mL) were added to a dry glass tube, followed by the addition of a THF solution of LDA (0.2 M, 0.2 mmol) with stirring at 0 °C. The reaction mixture was stirred at 0 °C for 15 minutes and then stirred at 0 °C for 1 hour under an oxygen atmosphere. The reaction was then quenched with water, extracted with DCM, and the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (hexane / DCM = 1 / 1 (volume ratio)).

[0160] 1 H NMR (500 MHz, CDCl3) δ 7.79(d, J = 7.78, 1H), 7.74(d, J = 7.78, 1H), 7.62(t, J = 7.78, 1H), 7.50(t, J = 7.55, 1H), 7.17(dd, J = 5.49, 2.28, 2H), 6.85(td, J = 0.91, 9.61, 2H), 6.24(d, J = 8.23, 1H), 4.84-4.71(m, 1.5H), 4.59(td, J = 0.91, 5.03, 12.5) 4.47(m, 0.5H). 13 C NMR (125 MHz, CDCl3) δ 162.65 (d, J = 162.652, 1C), 147.52, 134.20, 133.55, 132.74, 131.74, 130.78, 129.09(d, J = 8.67, 2C), 125.34, 115.72(d, J = 21.19, 2C), 85.13(d J = 85.13, 1C), 58.05(d, J = 18.30). 19 F NMR (470 MHz, CDCl3) δ -112.81, -225.13(dt, J = 23.12, 69.36).

[0161] (5) Synthesis of N-[2-fluoro-1-(4-fluorophenyl)ethyl]-N-(2-phenylethyl)-2-nitrobenzenesulfonamide (6)

[0162] [ka]

[0163] Compound 5b (34.2 mg, 0.1 mmol), triphenylphosphine (34.1 mg, 0.13 mmol), phenylethyl alcohol (15.6 μL, 0.13 mmol), and DCM (1 mL) were added to a dry glass tube, followed by a THF solution of DIAD (1.9 M, 0.13 mmol) with stirring at 0 °C. The reaction mixture was stirred at room temperature for 7 hours, and then the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (hexane / DCM = 1 / 4 (volume ratio)).

[0164] 1 H NMR (400 MHz, CDCl3) δ 8.04(dd, J = 7.78, 1.83, 1H), 7.74-7.63(m, 3H), 7.39(ddd, J = 1.83, 5.95, 3.66, 2H), 7.24-7.16(m, 3H), 7.09-6.99(m, 4H), 5.40(td, J = 5.49, 20.58, 1H), 4.92(m, 2H), 3.47(m, 2H), 2.82(m, 1H), 2.43(m, 1H). 13 C NMR (125 MHz, CDCl3) δ 162.78(d, J = 248.68, 1C), 148.23, 138.14, 133.86(2C), 131.78, 131.04, 130.10(d, J = 8.45, 2C), 128.77, 128.70, 126.74, 124.28, 116.03(d, J = 21.73, 2C), 82.74(d, J = 176.25, 1C), 59.14(d, J = 20.52, 1C), 47.88, 37.21. 19 F NMR (470 MHz, CDCl3) δ -112.43, -222.00(dt, J = 14.40, 50.38).

[0165] (6) Synthesis of N-[2-fluoro-1-(4-fluorophenyl)ethyl]-2-phenylethanamine (7)

[0166] [ka]

[0167] Compound 6 (44.6 mg, 0.1 mmol), potassium carbonate (41.5 mg, 0.3 mmol), benzenethiol (20.4 μL, 0.2 mmol), and acetonitrile (2 mL) were added to a dry glass tube. The reaction mixture was stirred at room temperature for 3 hours, and then the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (hexane / DCM = 1 / 1 (volume ratio)).

[0168] 1 H NMR (400 MHz, CDCl3) δ 7.31-7.16(m, 7H), 7.05-6.99(m, 2H), 4.47-4.23(m, 2H), 4.05-3.99(m, 1H), 2.81-2.70(m, 4H). 13 C NMR (125 MHz, CDCl3) δ 162,54(d, J = 246.27, 1C), 139.91, 134.33(dd, J = 7.85, 2.41, 1C), 129.35(d, J = 8.45, 2C), 128.79, 128.54, 126.29, 115.60(d, J = 21.73, 2C), 86.92(d, J = 175.04, 1C), 62.30(d, J = 19.31, 2C), 48.67, 36.52. 19 F NMR (470 MHz, CDCl3) δ -114.38, -218.57(dt, J = 14.40, 43.19).

[0169] [Example 5] An aminofluorinated product of styrene fluoride was synthesized using N-fluoro-N-(2-nitrobenzenesulfonyl)benzenesulfonamide synthesized in Example 3 as an aminofluorinating agent.

[0170] (1) Synthesis of N-(2-fluoro-1-(4-fluorophenyl)ethyl)-2-nitro-N-(phenylsulfonyl)benzenesulfonamide

[0171] [ka]

[0172] 1 H NMR (500 MHz, CDCl3) δ 8.28(s, 1H), 7.77-7.33(m, 10H), 6.96(dd, J = 8.59, 2H), 5.93(td, J = 6.87, 1H), 5.30-5.09(m, 2H). 13 C NMR (125 MHz, CDCl3) δ 162.99(d, J = 249.89), 148.36, 139.48, 134.87, 134.22, 132.97, 132.11, 131.86, 131.29(d, J = 8.45), 128.86, 128.72(d, J = 7.24), 128.57, 124.08, 115.77(d, J = 21.73), 82.46(d, J = 172.63), 62.50(d, J = 25.35). 19 F NMR (376 MHz, CDCl3) δ -111.72, -215.96.

[0173] (2) Synthesis of N-(2-fluoro-1-(4-fluorophenyl)ethyl)benzenesulfonamide

[0174] [ka]

[0175] The starting material (23.2 mg, 0.05 mmol), potassium carbonate (27.6 mg, 0.2 mmol), mercaptobenzoic acid (15.4 mg, 0.1 mmol), and DMF (1 mL) were added to a dry glass tube. The reaction mixture was stirred at room temperature for 4 hours, then quenched with water, partitioned with diethyl ether, and the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (hexane / DCM = 1 / 1 (volume ratio)).

[0176] 1 H NMR (400 MHz, CDCl3) δ 7.70(d, J = 8.00, 2H), 7.50(ddd, J = 1.37, 8.00, 1H), 7.38(dd, J = 7.32, 2H), 7.12-7.08(m, 2H), 6.88(ddd, J = 1.83, 8.69, 2H), 5.56(s, 1H), 4.63-4.39(m, 3H). 13 C NMR (101 MHz, CDCl3) δ 162.65(d, J = 247.57), 140.21, 132.86, 131.86, 129.13, 129.06, 127.16, 115.75(d, J = 22.16), 84.87(d, 178.21), 57.08(d, 19.27). 19 F NMR (376 MHz, CDCl3) δ -113.26, -223.39(ddd, J = 17.34, 46.24).

[0177] [Example 6] The amino fluorinating agent was synthesized according to the synthetic procedure described in Example 2.

[0178] (1) Synthesis of N-(2,4'-dinitro)benzenesulfonimide N-(2,2'-dinitro)benzenesulfonimide was obtained from 2-nitrobenzenesulfonamide (10.5 mmol) according to the procedure described above. Purification by silica gel column chromatography (DCM / MeOH = 1 / 0 to 10 / 1 (volume ratio)) afforded N-(2,4'-dinitro)benzenesulfonimide (4.00 g, 99% yield) as an orange solid.

[0179] [ka]

[0180] 1 H NMR (4 00 MHz, (CD3)2CO) δ 8.45(d, J = 8.7 Hz, 2H), 8.29(d, J = 6.9 Hz, 1H), 8.22(d, J = 8.7 Hz, 2H), 8.03-7.95(m, 3H). 13 C NMR (100 MHz, (CD3)2CO) δ 150.59, 147.66, 145.73, 135.35, 132.65, 132.45, 131.73, 128.93, 124.91, 124.25.

[0181] (2) Synthesis of N-fluoro-N-(2,4'-dinitro)benzenesulfonimide Following the procedure described above, N-fluoro-N-(2,4'-dinitro)benzenesulfonimide was obtained from sulfonimide (5.37 mmol) and purified by washing with hexane to give N-fluoro-N-(2,4'-dinitro)benzenesulfonimide (1.57 g, 72% yield) as a white solid.

[0182] [ka]

[0183] 1 H NMR (400 MHz, (CD3)2CO) δ 8.62 (ddd, J = 9.15, 2.29 Hz, 2H), 8.40 (ddd, J = 9.15, 2.29 Hz, 2H), 8.32 (dd, J = 7.78, 1.37 Hz, 1H), 8.25 (ddd, J = 7.78, 1.37 Hz, 1H), 8.15 (ddd, J = 8.00, 1.37, 0.91 Hz, 1H), 8.10 (ddd, J = 8.00, 1.37, 0.91 Hz, 1H) 13 C NMR (100 MHz, (CD3)2CO) δ 153.55, 149.69, 140.08, 134.18, 134.06, 132.70, 127.26, 126.61, 126.06, 19 F NMR (376 MHz, (CD3)2CO) δ -36.10 (s)

[0184] [Example 7] An aminofluorination reaction was carried out in the same manner as in Example 4, except that the compound (1a) (N-fluoro-N-(2-nitrobenzenesulfonyl)methanesulfonamide) synthesized in Example 2 was used as an aminofluorinating agent.

[0185] (1) Synthesis of N-[2-fluoro-1-(4-bromophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide The aminofluorination reaction was carried out using 4-bromostyrene (36.6 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product. The residue was purified by silica gel column chromatography (DCM / hexane = 1 / 1) to give N-[2-fluoro-1-(4-bromophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide as a white solid in 71% yield.

[0186] [ka]

[0187] 1 H NMR (400 MHz, (CD3)2CO) δ8.11(br, 1H), 7.99-7.85 (m, 3H), 7.61(d, J = 8.69, 2H), 7.47(d, J = 8.23, 2H), 5.94(td, J = 7.32, 12.81, 1H), 5.42-5.14(m, 2H), 3.17(s, 3H). 19 F NMR (470 MHz, CDCl3) δ -217.59(br).

[0188] (2) Synthesis of N-[2-fluoro-1-phenylethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide Styrene (20.8 mg, 0.2 mmol) was used as the substrate for the aminofluorination reaction, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-phenylethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide as a white solid in 89% yield.

[0189] [ka]

[0190] 1 H NMR (400 MHz, (CD3)2CO) δ8.06-7.83(m, 4H), 7.56(d, J = 6.87, 2H), 7.47-7.40(m, 3H), 5.99(td, J = 7.33, 13.28, 1H), 5.46-5.17(m, 2H), 3.02(s, 3H). 19 F NMR (471 MHz, CDCl3) δ -216.36(br).

[0191] (3) Synthesis of N-[2-fluoro-1-(4-methoxycarbonylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide The aminofluorination reaction was carried out using 4-methoxycarbonylstyrene (32.4 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(4-methoxycarbonylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide in 69% yield as a white solid.

[0192] [ka]

[0193] 19 F NMR (471 MHz, CDCl3) δ -216.23(br).

[0194] (4) Synthesis of N-[2-fluoro-1-(4-acetoxyphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide The aminofluorination reaction was carried out using 4-acetoxystyrene (32.4 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(4-acetoxyphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide as a white solid in 86% yield.

[0195] [ka]

[0196] 19 F NMR (376 MHz, CDCl3) δ -216.14(br).

[0197] (5) Synthesis of N-[2-fluoro-1-(4-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide The aminofluorination reaction was carried out using 4-methylstyrene (23.6 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(4-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide as a white solid in 99% yield.

[0198] [ka]

[0199] 19 F NMR (376 MHz, CDCl3) δ -217.19(br).

[0200] (6) Synthesis of N-[2-fluoro-1-(3-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide The aminofluorination reaction was carried out using 3-methylstyrene (23.6 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(3-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide as a white solid in 81% yield.

[0201] [ka]

[0202] 19 F NMR (376 MHz, CDCl3) δ -216.51(br).

[0203] (7) Synthesis of N-[2-fluoro-1-(2-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide The aminofluorination reaction was carried out using 2-methylstyrene (23.6 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(2-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide as a white solid in 67% yield.

[0204] [ka]

[0205] 1 H NMR (400 MHz, (CD3)2CO) δ8.11(br, 1H), 7.32(dd, J = 4.57, 1H), 7.14-7.12(br, 2H), 7.03(br, 1H), 6.19(m, 1H), 5.58(ddd, J = 9.61, 10.06, 48.03, 1H), 4.97(ddd, J = 9.61, 4.58, 44.71, 1H), 3.33(s, 3H), 2.40(s, 3H). 19 F NMR (376 MHz, (CD3)2CO) δ -218.28(br).

[0206] (8) Synthesis of N-[2-fluoro-2,3-dihydro-1H-inden-1-yl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide The aminofluorination reaction was carried out using indene (23.2 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-2,3-dihydro-1H-inden-1-yl]-N-(2-nitrobenzenesulfonyl)-methanesulfonamide in 99% yield as a white solid.

[0207] [ka]

[0208] 19 F NMR (471 MHz, (CD3)2CO) δ -162.28(s, 1F), -86.27(s, 1F).

[0209] [Example 8] An aminofluorination reaction was carried out in the same manner as in Example 4, except that N-fluoro-N-(2,4'-dinitro)benzenesulfonimide synthesized in Example 6 was used as the aminofluorinating agent.

[0210] (1) Synthesis of N-[2-fluoro-1-(4-fluorophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide The aminofluorination reaction was carried out using 4-fluorostyrene (24.4 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product. The residue was purified by silica gel column chromatography (DCM / hexane = 1 / 1) to give N-[2-fluoro-1-(4-fluorophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide in 94% yield as a white solid.

[0211] [ka]

[0212] 1 H NMR (400 MHz, (CD3)2CO) δ8.37 (d, J = 9.1 Hz, 2H), 8.24-8.11 (1H), 7.89-8.05 (m, 5H), 7.52 (q, J = 4.6 Hz, 2H), 7.15 (t, J = 8.9 Hz, 2H), 6.23-5.91 (1H), 5.34 (dd, J = 46.7, 8.2 Hz, 2H). 19 F NMR (376 MHz, (CD3)2CO) δ -112.72, -217.66.

[0213] One -SO2-Ph-NO2 was eliminated from the obtained N-[2-fluoro-1-(4-fluorophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide (compound (4ca)).

[0214] [ka]

[0215] Compound 4ca (52.7 mg, 0.1 mmol), potassium carbonate (27.7 mg, 0.2 mmol), benzenethiol (15.3 μL, 0.15 mmol), and acetonitrile (2 mL) were mixed in a dry glass tube. The resulting reaction mixture was stirred at room temperature for 3 hours, and then the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (DCM / hexane = 1 / 1) to give N-(2-fluoro-1-(4-fluorophenyl)ethyl)-4-nitrobenzenesulfonamide (compound 4cb).

[0216] Compound (4cb): 1 H NMR (400MHz, (CD3)2CO) δ 8.27(dt, J = 8.7, 2.8, 1.8, 2H), 7.96(dt, J = 9.2, 2.3, 2H), 7.31-7.36(m, 2H), 6.99(tt, J = 8.7, 2.3, 2H), 4.84-4.91(m, 1H), 4.58-4.65(m, 1H), 4.46-4.54(m, 1H). 13 C NMR (100 MHz, (CD3)2CO) δ 163.28(d, J = 244.4), 150.75, 148.22, 133.85, 130.40(d, J = 8.6), 129.27, 124.96, 116.07(d, J = 21.1), 85.5(d, J = 177.3), 58.21(d, J = 20.1). 19 F NMR (376 MHz, (CD3)2CO) δ -115. 61, -221.72(t, J = 46.2).

[0217] [ka]

[0218] Compound (4cb) (34.2 mg, 0.1 mmol), triphenylphosphine (65.6 mg, 0.25 mmol), phenylethyl alcohol (30.0 μL, 0.25 mmol), and DCM (1 mL) were added to a dry glass tube, followed by a THF solution of DIAD (1.9 M, 0.25 mmol) with stirring at 0 °C. The reaction mixture was stirred at room temperature for 3 hours, and then the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (hexane / DCM = 1 / 4 (volume ratio)) to give N-(2-fluoro-1-(4-fluorophenyl)ethyl)-4-nitro-N-phenethylbenzenesulfonamide (compound (4cc)).

[0219] Compound (4cc): 1 H NMR (400MHz, (CD3)2CO) δ 8.41(dt, J = 9.2, 2.3, 2H), 8.20(dt, J = 8.7, 2.8, 1.8), 7.43-7.47(m, 2H), 7.07-7.28(m, 9H), 5.45-5.52(m, 1H), 4.89-5.13(m, 2H), 3.39-3.58(m, 2H), 2.84-2.92(m, 1H), 2.56(td, J = 12.1, 5.5, 5.0, 1H). 13 C NMR (100 MHz, (CD3)2CO) δ163.55(d, J = 246.3), 151.11, 147.42, 139.34, 132.47, 131.35(d, J = 8.6), 129.73, 129.63, 129.47, 127.45, 125. 32, 116.51(d, J = 22.0), 82.79(d, J = 172.5), 60.54(d, J = 22.0), 48.23, 37.95. 19 F NMR (470 MHz, CDCl3) δ -114.63, -222.98(t, J = 46.2).

[0220] [ka]

[0221] In a dry glass tube, compound (4cc) (44.6 mg, 0.1 mmol), potassium carbonate (27.7 mg, 0.2 mmol), benzenethiol (15.3 μL, 0.15 mmol), and acetonitrile (2 mL) were added. The resulting reaction mixture was stirred at 40° C. for 3 hours, and then the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (hexane / DCM=1 / 1 (volume ratio)) to obtain N-[2-fluoro-1-(4-fluorophenyl)ethyl]-2-phenylethanamine (compound (7)).

[0222] Two -SO2-Ph-NO2 units were eliminated from compound (4ca).

[0223] [ka]

[0224] In a dry glass tube, compound 4ca (52.7 mg, 0.1 mmol), potassium carbonate (82.9 mg, 0.6 mmol), benzenethiol (40.8 μL, 0.4 mmol), and acetonitrile (2 mL) were mixed. The resulting reaction mixture was stirred at 40 °C for 3 h, and then the solvent was removed under vacuum. Boc anhydride (32.7 mg, 0.15 mmol), TEA (13.9 μL, 0.1 mmol), and DCM (2 mL) were added to the residue (containing compound 4cd). The resulting reaction mixture was stirred at 0 °C for 24 h, and then the solvent was removed under vacuum. The resulting residue was purified by silica gel column chromatography (hexane / DCM = 3 / 1 to 1 / 1 (volume ratio)) to give tert-butyl (2-fluoro-1-(4-fluorophenyl)ethyl)carbamate (compound 4ce).

[0225] Compound (4ce): 1 H NMR (500 MHz, CDCl3) δ 7.30(dd,J = 5.49, 3.20, 2H), 7.04(dd, J = 8.69, 2H), 5.15(s, 1H), 4.90(d, J = 21.96),4.70-4.49(m, 2H), 1.43(s, 9H). 13 C NMR (125 MHz, CDCl3) δ162.50(d, J = 247.47), 156.24, 134.36, 128.62(d, J = 8.45, 2C), 115.77(d, J = 21.73, 2C), 85.19(d, J = 176.25), 80.33, 54.12, 28.44(3C). 19 F NMR (470 MHz, CDCl3) δ -114.36(s), -226.66(d, J = 21.59).

[0226] (2) Synthesis of N-[2-fluoro-1-(4-bromophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide

[0227] The aminofluorination reaction was carried out using 4-bromostyrene (36.6 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(4-bromophenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide in 74% yield as a white solid.

[0228] [ka]

[0229] 1 H NMR (400 MHz, (CD3)2CO) δ 8.34-8.39 (m, 2H), 8.23 ​​(d, J = 7.8 Hz, 1H), 7.90-8.08 (m, 5H), 7.47-7.58 (m, 2H), 7.37-7.43 (m, 2H), 6.00-6.07 (m, 1H), 5.19-5.43 (m, 2H). 19 F NMR (376 MHz, (CD3)2CO) δ -217.86(td, J = 11.56, 46.24).

[0230] (3) Synthesis of N-[2-fluoro-1-phenylethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide

[0231] Styrene (20.8 mg, 0.2 mmol) was used as the substrate for the aminofluorination reaction, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-phenylethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide as a white solid in 64% yield.

[0232] [ka]

[0233] 1 H NMR (400 MHz, (CD3)2CO) δ 8.12-8.40 (m, 3H), 7.91-8.10 (m, 3H), 7.72 (dd, J = 40.3, 7.3 Hz, 2H), 7.33-7.51 (m, 5H), 5.96-6.09 (m, 1H), 5.13-5.52 (m, 2H). 19 F NMR (376 MHz, (CD3)2CO) δ -217.82 (td, J = 46.2, 11.6 Hz).

[0234] (4) Synthesis of N-[2-fluoro-1-(4-methoxycarbonylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide The aminofluorination reaction was carried out using 4-methoxycarbonylstyrene (32.4 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(4-methoxycarbonylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide in 57% yield as a white solid.

[0235] [ka]

[0236] 1 H NMR (400 MHz, (CD3)2CO) δ 8.29-8.36 (m, 3H), 7.72-8.13 (m, 7H), 7.57 (d, J = 7.8 Hz, 2H), 5.93-6.15 (m, 1H), 5.29-5.48 (m, 2H), 3.72-4.09 (m, 3H). 19 F NMR (376 MHz, (CD3)2CO) δ -217.79 (td, J = 46.2, 11.6 Hz).

[0237] (5) Synthesis of N-[2-fluoro-1-(4-acetoxyphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide The aminofluorination reaction was carried out using 4-acetoxystyrene (32.4 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(4-acetoxyphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide in 99% yield as a white solid.

[0238] [ka]

[0239] 1 H NMR (400 MHz, (CD3)2CO) δ 8.25-8.38 (m, 3H), 7.96-8.08 (m, 3H), 7.42-7.66 (m, 4H), 7.20 (dd, J = 30.6, 7.3 Hz, 2H), 6.01-6.08 (m, 1H), 5.22-5.45 (m, 2H), 2.26-2.34 (m, 3H). 19 F NMR (376 MHz, (CD3)2CO) δ -218.14 (t, J = 40.5 Hz).

[0240] (6) Synthesis of N-[2-fluoro-1-(4-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide The aminofluorination reaction was carried out using 4-methylstyrene (23.6 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(4-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide in 74% yield as a white solid.

[0241] [ka]

[0242] 1 H NMR (400 MHz, (CD3)2CO) δ 8.21-8.36 (m, 3H), 7.86-8.07 (m, 7H), 7.53-7.58 (m, 2H), 6.05-6.19 (m, 1H), 5.26-5.47 (m, 2H), 3.90 (s, 3H). 19 F NMR (376 MHz, (CD3)2CO) δ-217.77 (td, J = 46.2, 11.6 Hz).

[0243] (7) Synthesis of N-[2-fluoro-1-(3-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide The aminofluorination reaction was carried out using 3-methylstyrene (23.6 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(3-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide as a white solid in 77% yield.

[0244] [ka]

[0245] 19 F NMR (376 MHz, CDCl3) δ-217.57.

[0246] (8) Synthesis of N-[2-fluoro-1-(2-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide The aminofluorination reaction was carried out using 2-methylstyrene (23.6 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-1-(2-methylphenyl)ethyl]-N-(2-nitrobenzenesulfonyl)-4-nitrobenzenesulfonamide in 56% yield as a white solid.

[0247] [ka]

[0248] 19 F NMR (376 MHz, CDCl3) δ-215.51.

[0249] (9) Synthesis of N-[2-fluoro-2,3-dihydro-1H-inden-1-yl]-2-nitro-N-((4-nitrophenyl)sulfonyl)benzenesulfonamide The aminofluorination reaction was carried out using indene (23.2 mg, 0.2 mmol) as the substrate, and the solvent was removed to give a residue containing the aminofluorinated product, which was purified to give N-[2-fluoro-2,3-dihydro-1H-inden-1-yl]-2-nitro-N-((4-nitrophenyl)sulfonyl)benzenesulfonamide in 99% yield as a white solid.

[0250] [ka]

[0251] 19 F NMR (376 MHz, CDCl3) δ -160.85, -189.04. [Industrial Applicability]

[0252] The present invention provides an amino fluorinating agent capable of deprotecting substrates having unsaturated bonds under milder conditions than those used with NFSI, and an amination reaction using the amino fluorinating agent. The aminating agent of the present invention enables easy introduction of amino groups into a wide range of substrates, such as alkenes, allylic compounds, and aromatic compounds.< / nmr>

Claims

1. The following general formula (A1) 【Chemical 1】 [In the formula, R １ is C which may have a halogen atom １－３０ an alkyl group, or an optionally substituted phenyl group. A compound represented by the formula:

2. The R １ The compound according to claim 1, wherein is a methyl group or a 2-nitrophenyl group.

3. An amino fluorinating agent comprising the compound according to claim 1 as an active ingredient.

4. A compound having at least one unsaturated bond is used as a substrate, and a fluorine atom is introduced into one of the carbon atoms constituting at least one unsaturated bond formed between carbon atoms in the substrate using the amino fluorinating agent according to claim 3, and a compound represented by the following general formula (A1') is introduced into the other carbon atom: 【Chemistry 2】 [In the formula, R １ is C which may have a halogen atom １－３０ an alkyl group or an optionally substituted phenyl group. A method for producing an amino group-containing compound, comprising introducing a group represented by the formula:

5. The substrate is represented by the following general formula (B): 【Chemistry 3】 [In the formula, R １１ and R ２１ are each independently a hydrogen atom or a C １－３０ R is an aliphatic hydrocarbon group, an aryl group which may have a substituent, or a heteroaryl group which may have a substituent. １１ and R ２１ is C １－３０ When the aliphatic hydrocarbon group is an aliphatic hydrocarbon group, these C １－３０ The aliphatic hydrocarbon groups may be linked to each other to form a ring.] The method for producing an amino group-containing compound according to claim 4, wherein the compound is a compound represented by the formula:

6. R in the general formula (B) １１ and R ２１ one of which is a hydrogen atom and the other is a phenyl group which may have a substituent, The substituent is a halogen atom, C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Fluoroalkyl group, —(C═O)—OCH ３ and —O—(C═O)—CH ３ The method for producing an amino group-containing compound according to claim 5, wherein the compound is one or more selected from the group consisting of:

7. The following general formula (B) 【Chemistry 4】 [In the formula, R １１ and R ２１ are each independently a hydrogen atom or a C １－３０ R is an aliphatic hydrocarbon group, an aryl group which may have a substituent, or a heteroaryl group which may have a substituent. １１ and R ２１ is C １－３０ When the aliphatic hydrocarbon group is an aliphatic hydrocarbon group, these C １－３０ The aliphatic hydrocarbon groups may be linked to each other to form a ring.] to a compound represented by the following formula (A1-1): 【Chemistry 5】 is reacted as an amino fluorinating agent, and then a compound represented by the following formula (D-1) is reacted as an amino fluorinating agent. 【Chemistry 6】 The method for producing a primary amine comprises deprotecting an Ns group represented by the formula:

8. The following general formula (B) 【Chemistry 7】 [In the formula, R １１ and R ２１ are each independently a hydrogen atom or a C １－３０ R is an aliphatic hydrocarbon group, an aryl group which may have a substituent, or a heteroaryl group which may have a substituent. １１ and R ２１ is C １－３０ When the aliphatic hydrocarbon group is an aliphatic hydrocarbon group, these C １－３０ The aliphatic hydrocarbon groups may be linked to each other to form a ring.] to a compound represented by the following formula (A1-2): 【Chemistry 8】 as an amino fluorinating agent, and then reacting a compound represented by the following formula (D-2) 【Chemistry 9】 The Ms group represented by the following formula (D-1) is then deprotected. 【Chemistry 10】 and then deprotecting the Ns group.

9. The following general formula (A0) 【Chemistry 11】 [In the formula, R １ is C which may have a halogen atom １－３０ an alkyl group or an optionally substituted phenyl group, and X is a hydrogen atom or a lithium atom. to fluorinate a compound represented by the following general formula (A1): 【Chemistry 12】 [In the formula, R １ is the same as above] A method for producing a compound represented by the formula:

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